The primary objectives of this research project concern the cellular events responsible for the development and suppression of immune responses to antigen molecules. Toward this end, we aim to delineate the mechanisms of cooperative interactions between thymus- derived (T) lymphocytes and bone marrow-derived (B) cell precursors of antibody-forming cells in the development of such responses. These problems are being approached as directly as possible, utilizing both in vivo and in vitro systems and focusing primarily on the interactions between carrier-specific T cells and hapten-specific B cells in immune responses to hapten-carrier conjugates. In vivo systems designed to permit analysis of the relative degrees of the T cell regulatory influence involved in stimulation of B lymphocytes of the IgE as well as IgG and IgM antibody classes will be used. Evaluation of appropriate conditions conducive to development of enhancing and/or suppressive T cell influences on antibody production is of immediate priority, especially in terms of defining the antigen-specific vs. non-specific nature of T cell effects. We are also continuing to explore, both in vivo and in vitro, the critical genetic requirements for optimal T-B cell interactions with respect to the relevant genes in the histocompatibiliy gene complex that appear to dictate such restrictions. In vitro systems will be used to scrutinize various conditions capable of influencing triggering of specific T and B lymphocytes and to define the relevance of these influences to physiologic lymphocyte activation in vivo. We hope to elucidate the cellular target(s) and mechanisms of action of certain more commonly studied biologically active mediators such as thymosin, exdotoxin, supernates from mixed lymphocyte interactions, etc. We will continue to pursue our long range goals of analyzing in depth the cellular events occuring in the induction of various types of immunological tolerance employing both in vivo and in vitro systems. Studies of these types designed to develop a better understanding of the sub- or intracellular events involved in mechanisms of cell triggering and specific tolerance are ultimately directed toward the adaptation to potential therapeutic applications the capacity to effectively manipulate the humoral and cellular immune responses to a variety of antigens.